vitamin d supplementation in hiv-infected youth

Conditions: HIV Disease; Vitamin D Deficiency; Hypovitaminosis D; Hyperparathyroidism

Summary: along with its effects on bone metabolism, vitamin d is an important modulator of the immune system. experimental studies have shown that the active metabolite of vitamin d \[1,25(oh)2d\] is able to skew the t cell compartment into a more anti-inflammatory state, with inhibition of th1 and th17 cells and promotion of th2 and t regulatory subsets. in the context of hiv infection, in which th1 subpopulations are devoted to inhibit viral replication, any alteration of the th1/th2 balance would be of concern. the aim of this randomized controlled trial is to test wether oral supplementation with cholecalciferol could be able: 1) to improve vitamin d status and, 2) to play an immunomodulatory role, in vertically hiv-infected children and young adults with hypovitaminosis d.

there is increasing evidence that hypovitaminosis d is common in the general population. low dietary intake of vitamin d and reduced exposure to sunlight are probably the major risk factors. a high prevalence of hypovitaminosis d has been described in hiv-infected adults, and children. hiv infection itself and antiretroviral (arv) treatment may be responsible for alteration of vitamin d metabolism. for instance, studies have shown a significant decrease in serum 25-hydroxyvitamin-d \[25(oh)d\] concentration in adults receiving non-nucleoside reverse transcriptase inhibitors (nnrtis). whatever the cause(s) of hypovitaminosis d, because of the importance of vitamin d in bone health, randomized controlled trials (rct) have been performed to test whether vitamin d supplementation can improve vitamin d status and bone mineral metabolism in hiv-infected children and adolescents. along with its effects on bone metabolism, vitamin d is an important modulator of the immune system. the vitamin d receptor (vdr) is found in high concentrations in activated t lymphocytes, in small amounts in monocyte/macrophage cells while b lymphocytes do not contain detectable amounts of vdr. experimental studies have shown that the active di-hydroxylated metabolite of vitamin d \[1,25(oh)2d\] is able to skew the t cell compartment into a more anti-inflammatory state, with inhibition of th1 and th17 cells and promotion of th2 and t regulatory (treg) subsets. in the context of hiv infection, in which th1 subpopulations are devoted to inhibit viral replication, 16 any alteration of the th1/th2 balance would be of concern. although all the biological effects of vitamin d are mediated by the 1,25(oh)2d, it is the 25(oh)d to be routinely quantified because of its longer half-life.17 however, hiv-infected subjects may have a defective 1α-hydroxylation of 25(oh)d. thus, it is important to evaluate the effects of vitamin d supplementation both in terms of 25(oh)d and 1,25(oh)2d responses. this repeated-measures parallel-group rct is aimed to test wether a 12-month oral supplementation with cholecalciferol (vitamin d3) is able: 1) to increase serum 25(oh)d and 1,25(oh)2d levels and, 2) to affect t-cell phenotype in vertically hiv-infected children and young adults with hypovitaminosis d and stable hiv-disease. main outcome: to determine the frequency of hypovitaminosis d at 12-month of follow-up among subjects supplemented with oral cholecalciferol versus subjects receiving placebo. secondary outcome: to investigate correlations - if any - between serum vitamin d concentration and markers of immune activation (i.e. th1-, th2-, th17- and treg-lymphocytes count, t-lymphocyte vdr expression)

Eligibility criteria:
inclusion criteria: * vertically acquired hiv infection * age \< 30 years * serum 25(oh)d concentration \< 30 ng/ml * signed written informed consent exclusion criteria: * hyperparathyroidism, as detected by an intact serum parathyroid hormone (pth) ≥ 65 pg/ml * black ethnic group * any supplementation with vitamin d in the previous 12 months * use of any treatment known to alter vitamin d status in the previous 6 months (excluding arv) * any concomitant severe illness.

Keywords: hiv children adolescents vitamin d immunity t cell phenotype